Crosslinking of polyethylene for low wear using radiation and thermal treatments

ABSTRACT

The present invention discloses methods for enhancing the wear-resistance of polymers, the resulting polymers, and in vivo implants made from such polymers. One aspect of this invention presents a method whereby a polymer is irradiated, preferably with gamma radiation, then thermally treated, such as by remelting of annealing. The resulting polymeric composition preferably has its most oxidized surface layer removed. Another aspect of the invention presents a general method for optimizing the wear resistance and desirable physical and/or chemical properties of a polymer by crosslinking and thermally treating it. The resulting polymeric compositions is wear-resistant and may be fabricated into an in vivo implant.

This is a continuation of co-pending U.S. patent application Ser. No.09/795,229, filed on Feb. 26, 2001, entitled “CROSSLINKING OFPOLYETHYLENE FOR LOW WEAR USING RADIATION AND THERMAL TREATMENTS”, andallowed on Feb. 18, 2004, which is a continuation of application Ser.No. 09/214,586, filed on Jan. 6, 1999, and issued as U.S. Pat. No.6,228,900, on May 8, 2001, which is the national phase filing of PatentCooperation Treaty application number PCT/US97/11947, filed on Jul. 8,1997, which is based on U.S. provisional application Ser. No. 60/017,852filed on Jul. 9, 1996; Ser. No. 60/025,712 filed on Sep. 10, 1996; andSer. No. 60/044,390, filed on Apr. 29, 1997. The entire contents of thepredecessor applications are herein expressly incorporated by reference.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to polymers. It discloses methods forenhancing the wear-resistance of polymers by crosslinking and thermallytreating them. The polymers disclosed herein are useful for makingimplants, for example, as components of artificial joints such asacetabular cups.

BACKGROUND OF THE INVENTION

Ultrahigh molecular weight polyethylene (hereinafter referred to as“UHMWPE”) is commonly used to make prosthetic joints such as artificialhip joints. In recent years, it has become increasingly apparent thattissue necrosis and interface osteolysis, in response to UHMWPE weardebris, are primary contributors to the long-term loosening failure ofprosthetic joints. For example, wear of acetabular cups of UHMWPE inartificial hip joints introduces many microscopic wear particles intothe surrounding tissues. The reaction to these particles includesinflammation and deterioration of the tissues, particularly the bone towhich the prosthesis is anchored. Eventually, the prosthesis becomespainfully loose and must be replaced.

Improving the wear resistance of the UHMWPE socket and, thereby,reducing the rate of production of wear debris would extend the usefullife of artificial joints and permit them to be used successfully inyounger patients. Consequently, numerous modifications in physicalproperties of UHMWPE have been proposed to improve its wear resistance.

UHMWPE components are known to undergo a spontaneous, post-fabricationincrease in crystallinity and changes in other physical properties. (Seee.g., Rimnac, C. M., et al., J. Bone & Joint Surgery, 76-A(7):1052-1056(1994)). These changes occur even in scored (non-implanted) cups aftersterilization with gamma radiation, which initiates an ongoing processof chair scission, crosslinking, and oxidation or peroxidation involvingthe free radicals formed by the irradiation. These degradative changesmay be accelerated by oxidative attack from the joint fluid and cyclicstresses applied during use.

In an attempt to improve wear resistance, DePuy-DuPont Orthopaedicsfabricated acetabular cups from conventionally extruded bar stock thatpreviously had been subjected to heating and hydrostatic pressure thatreduced fusion defects and increased the crystallinity, density,stiffness, hardness, yield strength, and increased the resistance tocreep, oxidation and fatigue. Alternatively, silane cross-linked UHMWPE(XLP) has also been used to make acetabular cups for total hipreplacements in goats. In this case, the number of in vivo debrisparticles appeared to be greater for XLP than conventional UHMWPE cupimplants {Ferris, B. D., J. Exp. Path., 71:367-373 (1990)}.

Other modifications of UHMWPE have included: (a) reinforcement withcarbon fibers; and (b) post-processing treatments such as solid phasecompression molding. Indeed, carbon fiber reinforced polyethylene and aheat-pressed polyethylene have shown relatively poor wear resistancewhen used as the tibial components of total knee prosthesis. {See e.g.,Rimnac, C. M., et al., Trans. Orthopaedic Research Society, 17:330(1992)}.

Recently, several companies have modified the method of radiationsterilization to improve the wear resistance of UHMWPE components. Thishas typically involved packaging the polyethylene cups either in aninert gas (e.g., Howmedica, Inc.), in a partial vacuum (e.g., Johnson &Johnson, Inc.) or with an oxygen scavenger (e.g., Sulzer Orthopaedics,Inc.).

SUMMARY OF THE INVENTION

The present invention comprises two aspects:

The first aspect of the invention presents a method for increasing thewear resistance of a polymer by crosslinking the polymer, followed bythermally treating the crosslinked polymer. Non-limiting examples of thethermal treatments are remelting or annealing. Preferably, the polymeris crosslinked by gamma irradiation in the solid state prior to beingmodified to a desired final form or shape of the final product. In thepreferred embodiment, the surface layer of the crosslinked and thermallytreated polymer, which is the most oxidized and least crosslinked partof the polymer, is removed, e.g., in the process of machining the finalproduct out of the irradiated bar and thermally treated bar or block.The radiation dose is also preferably adjusted so that the optimal doseoccurs within the solid polymer bar or block at the level of the bearingsurface of the final product. Also presented are the polymers made fromthis method; methods for making products (e.g., in vivo implants) fromthese polymers; and the products (e.g., in vivo implants) made fromthese polymers.

The second aspect of the invention provides a systematic method fordetermining an optimal balance among wear resistance and other physicaland/or chemical properties that are deemed important to the long-termperformance of an implant in vivo, and applying this optimal balance todetermine the appropriate crosslinking and thermal treatment conditionsfor processing a polymer. A flowchart is provided as a non-limitingillustration of the method for determining the optimal balance. Alsoprovided are methods for treating polymers which apply the aboveappropriate crosslinking and thermal treatment conditions; the polymersproduced by these methods; methods for making products (e.g., in vivoimplants) from these polymers; and the products (e.g., in vivo implants)made from these polymers.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 presents the degree of crystallinity vs. depth at indicated dosesfor UHMWPE that was irradiated in a vacuum (i.e., a low-oxygenatmosphere).

FIG. 2 presents the gel content vs. depth at indicated doses for UHMWPEthat was irradiated in a vacuum (i.e., a low-oxygen atmosphere).

FIG. 3 presents the gel content vs. depth at indicated conditions forUHMWPE.

FIG. 4 presents the degree of crystallinity vs. depth at indicatedconditions for UHMWPE.

FIG. 5 presents the gel content vs. depth at indicated conditions forUHMWPE.

FIG. 6 presents the shape of the acetabular cup fabricated from theirradiated UHMWPE.

FIG. 7 presents a schematic diagram of the hip joint simulator used inthe wear tests.

FIG. 8 presents the wear by volume loss of each cup of the fourmaterials. Upper curves: 3.3 Mrad; Lower curves: 28 Mrad.

FIG. 9 presents the curves of the average volumetric wear and standarddeviations of three cups of each material at each interval.

FIG. 10 presents the oxidation profile as a function of depth at variousaging times.

FIG. 11 presents the oxidation profile as a function of depth at variousaging times.

FIG. 12 presents the oxidation profile as a function of depth at variousaging times.

FIG. 13 presents the oxidation profile as a function of depth at variousaging times.

FIG. 14 presents the oxidation profile as a function of depth forvarious materials. The specimens were stored in air for 5 months andthen aged for 20 days at 80° C.

FIG. 15 presents gel content as a function of depth at various agingtimes.

FIG. 16 presents gel content as a function of depth at various agingtimes.

FIG. 17 presents gel content as a function of depth at various agingtimes.

FIG. 18 presents gel content as a function of depth at various agingtimes.

FIG. 19 presents the degree of crystallinity as a function of depthafter 30 days' aging.

FIG. 20 shows the combined soak-corrected wear for the non-aged and agedcups.

FIG. 21 shows the individual wear for cups irradiated at differentdoses.

FIG. 22 shows the average wear rate versus radiation dose ofnon-remelted and remelted cups.

FIGS. 23A and 23B present the flowchart illustrating the optimizationmethod of the present invention.

FIG. 24 graphically shows the oxidation profiles for irradiated andremelted UHMWPE as a function of depth from the UHMWPE bar surface.

FIG. 25 graphically shows the tensile strength at yield versus radiationdose of irradiated UHMWPE with or without remelting, and non-irradiatedand not remelted UHMWPE.

FIG. 26 graphically shows the tensile strength at break versus radiationdose of irradiated UHMWPE with or without remelting, and non-irradiatedand not remelted UHMWPE.

FIG. 27 graphically shows the elongation at break versus radiation doseof irradiated UHMWPE with or without remelting, and non-irradiated andnot remelted UHMWPE.

DETAILED DESCRIPTION OF THE INVENTION

Abbreviations used in this application are as follows: UHMW ultra-highmolecular weight UHMWPE ultra-high molecular weight polyethylene HMWhigh molecular weight HMWPE high molecular weight polyethylene

The present invention contains two aspects. The first aspect of theinvention provides methods for improving the wear resistance of apolymer by crosslinking (preferably the bearing surface of the polymer)and then thermally treating the polymer, and the resulting novelpolymer. Preferably, the most oxidized surface of the polymer is alsoremoved. Also presented are the methods for using the polymericcompositions for making products and the resulting products, e.g., invivo implants. Specific examples of this method are presented in thesection: “I. First Aspect of the Invention: Polymeric Compositions withIncreased Wear Resistance” and “I (A) Further Examples of the FirstAspect of the Invention”, below.

The method of the invention utilizes irradiation for crosslinking apolymer followed by thermal treatment to decrease the free radicals toproduce a preformed polymeric composition. The term “preformed polymericcomposition” means that the polymeric composition is not in a finaldesired shape or form (i.e., not a final product). For example, wherethe final product of the preformed polymeric composition is anacetabular cup, irradiation and thermal treatment of the polymer couldbe performed at pre-acetabular cup shape, such as when the preformedpolymeric composition is in the form of a solid bar or block.

A second aspect of the invention provides a systematic method (anexample of which is illustrated in the flowchart, below) for determiningthe optimal parameters for the above mentioned crosslinking and thermaltreatment. This second aspect provides a method for determining themaximum possible improvement in wear resistance, consistent with keepingthe other physical and/or chemical propert(ies) within the user'sdesired limits, with the least amount of trial and error testing. Oncethe optimal parameters (i.e., crosslinking conditions such as radiationdose when radiation is used to crosslink the polymer, and thermaltreatment parameters) are determined by this method, the polymer willthen be processed according to the optimal parameters. Thus, thisprotocol renders the development of a preformed polymeric compositionwith particular chemical/mechanical characteristics routine withoutresort to undue experimentation. Also presented are the methods forusing the preformed polymeric composition for making products, and theproducts, e.g., in vivo implants.

In the present invention, the wear resistance of the polymer is improvedby crosslinking. The crosslinking can be achieved by various methodsknown in the art, for example, by irradiation from a gamma radiationsource or from an electron beam, or by photocrosslinking. The preferredmethod for crosslinking the polymer is by gamma irradiation. The polymeris preferably crosslinked in the form of an extruded bar or moldedblock.

In the preferred method, the crosslinked polymer is subjected to thermaltreatment such as by remelting (i.e., heated above the meltingtemperature of the crosslinked polymer) or annealing (i.e., heated atbelow the melting temperature of the crosslinked polymer) to produce thepreformed polymeric composition.

In the preferred embodiment of both the first and second aspects of theinvention, the outer layer of the resulting preformed polymericcomposition, which is generally the most oxidized and least crosslinkedand, thus, least wear resistant, is removed. For example, the bearingsurface of the preformed polymeric composition may be fashioned frominside, e.g., by machining away the surface of the irradiated andthermally treated composition before or during fashioning into the finalproduct, e.g., into an implant. Bearing surfaces are surfaces which arein moving contact with another, e.g., in a sliding, pivoting, orrotating relationship to one another.

Choices of Polymers

The polymers are generally polyester, poly(methylmethacrylate), nylon,polycarbonates, and polyhydrocarbons such as polyethylene, andpolypropylene. High molecular weight (HMW) and ultra-high molecularweight (UHMW) polymers are preferred, such as HMW polyethylene (HMWPE),UHMW polyethylene (UHMWPE), and UHMW polypropylene. HMW polymers havemolecular weights ranging from about 10⁵ grams per mole to just below10⁶. UHMW polymers have molecular weights equal to or higher than 10⁶grams per mole, preferably from 10⁶ to about 10⁷. The polymers aregenerally between about 400,000 grams per mole to about 10,000,000 andare preferably polyolefinic materials.

For implants, the preferred polymers are those that are wear resistantand have exceptional chemical resistance. UHMWPE is the most preferredpolymer as it is known for these properties and is currently widely usedto make acetabular cups for total hip prostheses and components of otherjoint replacements. Examples of UHMWPE are those having molecular weightranging from about 1 to 8×10⁶ grams per mole, examples of which are: GUR4150 or 4050 (Hoechst-Celanese Corporation, League City, Tex.) with aweight average molecular weight of 5 to 6×10⁶ grams per mole; GUR 4130with a weight average molecular weight of 3 to 4×10⁶; GUR 4120 or 4020with a weight average molecular weight of 3 to 4×10⁶; RCH 1000(Hoechst-Celanese Corp.) with a weight average of molecular weight of4×10⁶ and HiFax 1900 of 2 to 4×10⁶ (HiMont, Elkton, Md.). Historically,companies which make implants have used polyethylenes such as HIFAX1900, GUR 4020, GUR 4120 and GUR 4150 for making acetabular cups.

Sterilization Methods

All polymeric products must be sterilized by a suitable method prior toimplanting in the human body. For the formed crosslinked and thermallytreated polymeric compositions (i.e., the final products) of the presentinvention, it is preferable that the products be sterilized by anon-radiation based method, such as ethylene oxide or gas plasma, inorder not to induce additional crosslinking and/or oxidation of thepreviously treated preformed polymeric composition. Compared toradiation sterilization, a non-radiation sterilization method has aminor effect on the other important physical characteristics of theproduct.

Nevertheless, the method can be used in conjunction with radiationsterilization. If the final products are to be sterilized by anadditional dose of radiation, it is preferable to take into account theeffect of this additional radiation dose on the wear resistance andother properties of the polymer, in determining the optimum radiationdose used in the initial crosslinking. Furthermore, it is preferablethat the radiation sterilization be done while the final product (e.g.,in vivo implant) is packed in a suitable low-oxygen atmosphere (e.g., inpartial vacuum, in an inert gas such as nitrogen, or with an oxygenscavenger included) in order to minimize oxidation of the surface layerof the final product during and after sterilization by irradiation.

The dose ranges in this application do not take into account radiationsterilization. If radiation sterilization is used, then the dose rangesmay have to be adjusted. Such adjustment can be easily performed usingthe teachings herein. For example, if after comparing the dose-responsecurves for wear with those for other important physical or chemicalproperties, it is determined that the optimal total radiation dose is 8Mrad, and it is intended to sterilize the polymer with 2.5 Mrad gammaradiation (the minimum industrial standard sterilization dose), then theinitial radiation dose (before sterilization) should be 5.5 Mrad, suchthat the total dose (initial plus sterilization doses) will be 8 Mrad.These calculations are approximate, since the total crosslinkingachieved will not be exactly equivalent to a single 8 Mrad dose.

Nevertheless, the applicants have discovered that a high level ofcrosslinking in the surface layer of a polymer markedly reduces thedegradative effects of surface oxidation, i.e., that would otherwiseoccur if a non-pre-crosslinked polymer were irradiated in the presenceof oxygen (for example, see FIG. 3).

Methods for Characterizing the Polymers

The degree of crystallinity can be determined using methods known in theart, e.g. by differential scanning calorimetry (DSC), which is generallyused to assess the crystallinity and melting behavior of a polymer.Wang, X. & Salovey, R., J. App. Polymer Sci., 34:593-599 (1987).

Wide-angle X-ray scattering from the resulting polymer can also be usedto further confirm the degree of crystallinity of the polymer, e.g. asdescribed in Spruiell, J. E., & Clark, E. S., in “Methods ofExperimental-Physics”, L. Marton & C. Marton, Eds., Vol. 16, Part B,Academic Press, New York (1980). Other methods for determining thedegree of crystallinity of the resulting polymer may include FourierTransform Infared Spectroscopy {Painter, P. C. et al., “The Theory OfVibrational Spectroscopy And Its Application To Polymeric Materials”,John Wiley and Sons, New York, U.S.A. (1982)}and density measurement(ASTM D150568). Measurements of the gel content and swelling aregenerally used to characterize crosslink distributions in polymers, theprocedure is described in Ding, Z. Y., et al., J. Polymer Sci., PolymerChem., 29:1035-38 (1990). FTIR can also be used to assess the depthprofiles of oxidation as well as other chemical changes such asunsaturation {Nagy, E. V., & Li, S., “A Fourier transform infraredtechnique for the evaluation of polyethylene orthopaedic bearingmaterials”, Trans. Soc. for Biomaterials, 13:109 (1990); Shinde, A. &Salovey, R., J. Polymer Sci., Polym. Phys. Ed., 23:1681-1689 (1985)}.

Use of Crosslinked Polymers for Implants

Another aspect of the invention presents a process for making implantsusing the preformed polymeric composition of the present invention. Thepreformed polymeric composition may be shaped, e.g., machined, into theappropriate implants using methods known in the art. Preferably, theshaping process, such as machining, removes the oxidized surface of thecomposition.

Preformed Polymeric Compositions

The preformed polymeric compositions of the present invention can beused in any situation where a polymer, especially UHMWPE, is called for,but especially in situations where high wear resistance is desired. Moreparticularly, these preformed polymeric compositions are useful formaking implants.

Implants Made of Crosslinked Polymers

An important aspect of this invention presents implants that are madewith the above preformed polymeric compositions or according to themethods presented herein. In particular, the implants are produced frompreformed polymeric composition are UHMW polymers crosslinked by gammaradiation followed by remelting or annealing, removing the oxidizedsurface layer and then fabricating into a final shape. The preformedpolymeric composition of the present invention can be used to makeimplants for various parts of the body, such as components of a joint inthe body. For example, in the hip joints, the preformed polymericcomposition can be used to make the acetabular cup, or the insert orliner of the cup, or trunnion bearings (e.g. between the modular headand the stem). In the knee joint, the preformed polymeric compsition canbe used to make the tibial plateau (femoro-tibial articulation), thepatellar button. (patello-femoral articulation), and trunnion or otherbearing components, depending on the design of the artificial kneejoint. In the ankle joint, the preformed polymeric composition can beused to make the talar surface (tibio-talar articulation) and otherbearing components. In the elbow joint, the preformed polymericcomposition can be used to make the radio-numeral joint, ulno-humeraljoint, and other bearing components. In the shoulder joint, thepreformed polymeric composition can be used to make the glenoro-humeralarticulation, and other bearing components. In the spine, the preformedpolymeric composition can be used to make intervertebral diskreplacement and facet joint replacement. The preformed polymericcomposition can also be made into temporo-mandibular joint (jaw) andfinger joints. The above are by way of example, and are not meant to belimiting.

The following discusses the first and second aspects of the invention inmore detail.

I. First Aspect of the Invention: Polymeric Compositions with IncreasedWear Resistance

The first aspect of the invention provides preformed polymericcompositions which are wear resistant and useful for making in vivoimplants. In this aspect, for polymers in general, and more preferablyUHMW and HMW polymers, and most preferably UHMWPE and HMWPE, theirradiation dose is preferably from about 1 to about 100 Mrad, and morepreferably, from about 5 to about 25 Mrad, and most preferably fromabout 5 to about 10 Mrad. This most preferable range is based onachieving what the inventors have determined to be a reasonable balancebetween improved wear resistance and minimal degradation of otherimportant physical properties.

In vivo implants of the present invention, i.e., irradiated within theabove dose ranges are expected to function in vivo without mechanicalfailure. The UHMWPE acetabular cups used by Oonishi et al. [in Radiat.Phys. Chem., 39: 495-504 (1992)] were irradiated to 100 Mrad andfunctioned in vivo without reported mechanical failure after as long as26 years of clinical use. Furthermore, it is surprising that, as shownin the EXAMPLES, acetabular cups from the preformed polymericcomposition prepared according to the present invention, but irradiatedto much less than 100 Mrad, exhibited much higher wear resistance thanreported by Oonishi et al.

On the other hand, if a user is primarily concerned with reducing wear,and other physical properties are of secondary concern, then a higherdose than the above stipulated most preferable range (e.g., 5 to 10Mrad) may be appropriate, or vice versa (as illustrated in the detailedexamples in the following section). The optimum radiation dose ispreferably based on the dose received at the level of the bearingsurface in the final product. Gamma radiation is preferred.

The irradiated polymer is then preferably remelted at or above meltingtemperature of the irradiated polymer, e.g., in air. As used herein, themelting temperature of the crosslinked or irradiated polymer isidentified from the peak of the melting endotherm as measured by DSC.Preferably, the remelting temperature is from about the meltingtemperature of the irradiated polymer to about 100° C. to about 160° C.above the melting temperature of the irradiated polymer; more preferablyfrom about 40° C. to about 80° C. above the melting temperature of theirradiated polymer; and most preferably from about 1° C. to about 60° C.above the melting temperature of the irradiated polymer. For example, inthe case of UHMWPE, the remelting temperature is preferably from about136° C. to about 300° C., more preferably from about 136° C. to about250° C., and most preferably from about 136° C. to about 200° C.Specific conditions for remelting are described in EXAMPLES 1 and 2,below.

Generally, in practice, the remelting temperature is inverselyproportional to the remelting period. The polymer is preferably remeltedover a period from about 1 hour to about 2 days, more preferably fromabout 1 hour to about 1 day, and most preferably from about 2 hours toabout 12 hours.

Since, depending on the time and temperature applied, annealing canproduce less of an effect than remelting on physical properties such ascrystallinity, yield strength and ultimate strength, annealing may beused in place of remelting as a means for reducing the free radicalsremaining in the polymer after irradiation crosslinking, in order tomaintain these physical properties within limits required by the user.Thermal treatment, such as remelting or annealing, removes free radicalsand thereby improves long term wear resistance of the polymer. On theother hand, annealing is slower and thus takes longer than remelting,making it likely to be more expensive in industrial applications.

The annealing temperature is preferably from about room temperature tobelow the melting temperature of the irradiated polymer; more preferablyfrom about 90° C. to about 1° C. below the melting temperature of theirradiated polymer; and most preferably from about 60° C. to about 1° C.below the melting temperature of the irradiated polymer. For example,UHMWPE may be annealed at a temperature from about 25° C. to about 135°C., preferably from about 50° C. to about 135° C., and more preferablyfrom about 80° C. to about 135° C. The annealing period is preferablyfrom about 2 hours to about 7 days, and more preferably from about 7hours to about 5 days, and most preferably from about 10 hours to about2 days.

Instead of using the above range of radiation dose as a criterion, theappropriate amount of crosslinking may be determined based on the degreeof swelling, gel content, or molecular weight between crosslinks afterthermal treatment. This altenative is based on the applicant's findings(detailed below) that acetabular cups made from UHMWPE falling within apreferred range of these physical parameters have reduced ornon-detectable wear. The ranges of these physical parameters include oneor more of the following: a degree of swelling of between about 1.7 toabout 5.3; molecular weight between crosslinks of between about 400 toabout 8400 g/mol; and a gel content of between about 95% to about 99%. Apreferred polymer or final product has one or more, and preferably all,of the above characteristics. These parameters can also be used asstarting points in the second aspect of the invention (as illustrated bythe flowchart, discussed below) for determining the desired radiationdose to balance the improvement in wear resistance with other desiredphysical or chemical properties, such as polymer strength or stiffness.

After crosslinking and thermal treatment, preferably, the most oxidizedsurface of the preformed polymeric composition is removed. The depthprofiles of oxidation of the preformed polymeric composition can bedetermined by methods known in the art, such as FTIR, described aboveand in EXAMPLES 3 and 6. In general, to remove the most oxidizedsurface, preferably a minimum of about 0.5 mm to 1.0 mm of the surfaceof preformed polymeric composition which is exposed to air is removed,e.g. by machining, before or while fashioning the preformed polymericcomposition into the final product.

I. (A) Further Examples of the First Aspect of the Invention

As noted above, the most preferable range of dose for crosslinkingradiation (i.e., from 5 to 10 Mad) was based on achieving what theinventors have determined to be a reasonable balance between improvedwear resistance and minimal degradation of other important physicalproperties. The following examples illustrate applications of thepresent invention with altenative criteria for the optimal dose. Theseexamples use in vivo implants as non-limiting examples of the products,and UHMWPE or HMWPE bar or block as a non-limiting example of a startingmaterial.

In the first example, the user desires to achieve a minimum wear rate ofthe in vivo implant made from the UHMWPE and HMWPE, and the otherphysical or chemical properties are important but of lesser concern. Insuch a case, the user may choose to irradiate the UHMWPE and HMWPE baror block between about 15 Mrad to about 20 Mrad (as shown by FIG. 22).As discussed in the section “II(b) Application of the Flowchart”, below,GUR 4150 is representative of UHMWPE and HMWPE. The irradiated UHMWPE orHMWPE bar or block is further remelted or annealed at a temperature andtime described in “I. First Aspect of the Invention: PolymericCompositions with Increased Wear Resistance”, above.

In a second example, the user may wish to produce an UHMWPE which is aswear resistant as possible while meeting the tensile strength at break(ultimate), tensile strength at yield, and elongation at break criteriaof the standard specified by the American Society for Testing andMaterials F-648 standard (hereinafter referred to as “ASTM F648”) forUHMWPE for in vivo use. The information about this standard can be foundin a current issue of the Annual Book of ASTM Standards, Medical Devicesand Services, “Standard Specification for Ultra-High-Molecular-WeightPolyethylene Powder and Fabricated Form for Surgical Implants”, AmericanSociety for Testing and Materials. The method of the second aspect ofthe present invention (as illustrated by the flowchart) may be used toadjust the crosslinking and thermal treatment parameters to meet anycurrent ASTM F648 criteria.

For example, to meet the 1996 ASTM F648 (F648-96) criteria for Type 1 or2 UHMWPE, the UHMWPE must have: a tensile strength at break (ultimate)of at least 35 MPa (for Type 1) and 27 MPa (for Type 2) at 23° C. and5.08 cm/min; a tensile strength at yield of at least 21 MPa (Type 1) and19 MPa (for Type 2) at 23° C., and 5.08 cm/min; and elongation at breakof at least 300% at 5.08 cm/min. The test conditions are described inASTM D638, Type IV (Annual Book of ASTM Standards, American Society forTesting and Materials). Alternatively, to meet the 1996 ASTM F648criteria for Type 3 UHMWPE, the UHMWPE must have: a tensile strength atbreak (ultimate) of at least 27 MPa at 23° C. and 5.08 cm/min; a tensilestrength at yield of at least 19 MPa at 23° C., and 5.08 cm/min; andelongation at break of at least 250% at 5.08 cm/min.

The plots of mechanical properties vs irradiation dose for GUR 4150(which is representative of Type 2 UHMWPE) (FIGS. 25-27) show that, forall of the radiation doses between 5 to 25 Mrad, the above ASTM F648criteria for Types 2 UHMWPE are fulfilled except for the elongation atbreak, which crosses the 300 limit at about 6 Mrad. Thus, if the ASTMF648 criteria are to be met for Types 2 UHMWPE, the maximum (i.e., themost preferred) gamma radiation dose is about 6 Mrad. As illustrated inthe second aspect of the invention (following section), thecorresponding curves of wear and other physical properties vs.crosslinking dose could be used to determine the preferred dose rangefor other Types of UHMWPE or for other polymers in general.

II. Second Aspect of the Invention: Method for Optimizing WearResistance and Desirable Physical and/or Chemical Characteristics of aPolymeric Composition

The second aspect of the invention uses the findings in this patentapplication (including those presented in the “EXAMPLES” section, below)to construct a method which allows one skilled in the art, tosystematically identify the conditions necessary to routinely produce apolymer with an optimal balance of wear resistance and physical and/orchemical properties, with minimal additional testing and minimal trialand error. In one embodiment of this aspect of the invention, theoptimizing method can be schematically illustrated in a flowchart. Oncethe optimal conditions have been determined by this method, the polymercan then be subjected to these conditions for processing.

The present invention is based in part, on the discovery that wear ratedecreases with increasing radiation dose, and there is a maximum doseabove which there is little or no additional improvement in wear, buthigher doses might degrade other important physical and/or chemicalproperties of the polymer, such as yield or ultimate strength,elongation to failure, impact strength or fatigue resistance, as well asincreasing the susceptibility to oxidation. Oxidation, in turn, is knownto adversely affect one or more of these physical properties, and wasshown to occur in the examples below for UHMWPE crosslinked at a doseaveraging about 28 Mrad if there had been no thermal treatment.Consequently, a polymer irradiated at a high radiation dose may exhibitimproved wear resistance, but its other physical or chemical propertiesmay fall outside of desirable or allowable limits, such as thosespecified by ASTM F648 for UHMWPE for in vivo use.

The method is also based in part on the discovery that, while otherimportant physical properties (such as crystallinity or elongation tobreak) may be markedly affected by the amount of thermal treatment(e.g., remelting or annealing) applied to the polymer after irradiationcrosslinking, the wear resistance is not markedly affected. This latterdiscovery permits reducing the amount of additional testing required bythe user in order to identify the crosslinking dose which will providethe user's desired balance among wear resistance and other physicalproperties. This method is useful, e.g., in the case where performedpolymeric composition made of UHMWPE is used for making in vivoimplants, such as acetabular cups.

II (a) Summary of the Steps of the Optimization Method

Thus, the second aspect of the present invention provides a systematicmethod for optimizing the balance among wear resistance and otherdesired physical and/or chemical characteristics of a polymer. The stepsin this method are summarized in the non-limiting example of theflowchart of FIGS. 23A and 23B. In the flowchart and the followingdiscussion, for ease of discussion, irradiation is used as an example ofa crosslinking method, and implant is used as an example of the productthat is made from the polymer. However, as discussed elsewhere in thisapplication, other crosslinking methods and products may be used.

-   Step 1: The process typically begins with the polymer in solid form,    such as an extruded bar or block.-   Step 2: The bar is irradiated over a range of doses up to the    maximum that is likely to produce a material with the desired wear    resistance and physical and/or chemical properties. This irradiation    may be done, for example, in the case of gamma radiation by means of    a cobalt 60 gamma radiation facility as is presently used for    industrial-scale sterilization of implants.-   Step 3: The irradiated bars are then remelted. Applicants found that    remelting of an irradiated polymer would substantially reduce the    free radicals produced during irradiation, thus minimizing long-term    oxidation and chain scission. By improving the polymeric    composition's resistance to long-term oxidation, remelting also    improves the polymeric composition's long-term resistance to wear.    For further discussion of the subject, see EXAMPLES 2, 3, and 4,    below

Although the bar may be contained in a low-oxygen atmosphere during theremelting, this may not be essential since, even if the bar is remeltedin ambient air, the resultant oxidation may affect only the surfacelayer of the polymer (e.g. in the following EXAMPLE section, FIGS. 2, 5,and 24, show oxidation extending to about 1 mm deep). In the preferredembodiment of the invention, the oxidized surface layer of the preformedpolymeric composition will be removed, e.g., during subsequent machiningof the products out of the treated bar.

-   Step 4A The radiation dose is correlated with the wear resistance of    the products made from the irradiated remelted polymeric    composition, as determined in a wear test that adequately simulates    the wear conditions of the products. For example, if the polymeric    composition will be made into an implant, then the wear test should    preferably adequately simulate the wear conditions of such implants    in vivo. The correlation may be arrived at by plotting a    dose-response curve for irradiation dose vs. wear.-   Step 4B: Similarly, the radiation dose is correlated with each of    the physical and/or chemical properties that may be markedly    affected by the radiation dose and that might, in turn,    substantially affect the performance of the implant in vivo, both    for non-remelted and remelted polymer. Again, the correlation may be    arrived at by plotting a dose-response curve for irradiation dose    vs. each of these physical and/or chemical properties.

The user does not have to do dose vs. properties for each property thatmight be affected, but only those properties that are consideredimportant for the proper functioning of the implant in vivo. Which ofthese properties are important for the intended application, and thelimiting values of these properties, may vary for different polymericcompositions and for different types of applications (e.g., hipprostheses compared to knee prostheses) and must, therefore, beestablished by the user before applying the flowchart.

-   Step 5 is the first attempt at optimization. The user may first    decide on the desired amount of improvement in the wear resistance,    i.e., the maximum wear rate that is permissible for the user's    application. The dose-response curve for wear (Step 4A) then shows    the minimum radiation dose necessary to provide this amount of    improvement in wear resistance.

Similarly, the dose response curves for the other physical or chemicalproperties deemed critical or important (Step 4B) provide the values ofthese properties corresponding to the specific radiation dose identifiedin Step 4A as being necessary to provide the desired improvement in wearresistance. It each of these other physical or chemical properties arewithin allowable limits for the crosslinked and remelted polymer, thenan optimal method has been identified (Step 6). In other words, theimplant can be made by irradiating the solid polymer bar, remelting thebar and machining out the implant; the entire process being conductedsuch that the resulting implant has received the optimal dose at itsbearing surface.

Alternatively, the user may first decide on critical values for one ormore properties, such as ultimate tensile strength, fatigue strength,etc., and then check the corresponding dose response curves for theremelted polymer for the maximum allowable dose, and then check the wearvs. dose curve to determine whether this dose gives sufficientimprovement in wear (i.e., the user does not necessarily have to beginby choosing the desired amount of improvement in wear).

However, if not enough improvement in wear will be obtained whilekeeping these other chemical and physical properties within allowablelimits, or conversely, if the dose required for the desired wearimprovement causes one or more of these properties to be out ofallowable limits, then the user can use a lower radiation dose (i.e.,accept a higher wear rate) if he wishes to remelt the materials or,alternatively, annealing may be substituted for remelting (Step 7). Fora crosslinked material, annealing is less efficient than remelting inremoving free radicals, but may cause less of a reduction in otherimportant physical properties.

Whether annealing is a practical option will be apparent from thedose-response curves for the non-remelted and remelted polymers. Thatis, if the desired value of the property in question falls between thetwo curves (see for example, FIGS. 25 and 26), then a polymer with thedesired limiting value may be produced by an annealing process with anappropriate time/temperature combination.

It is not necessary to generate additional wear dose-response curves foreach of the many possible combinations of annealing time andtemperature. It is expected that the radiation dose necessary to producethe desired reduction in wear that is determined from the weardose-response curve for remelted polymer in Step 4A, will also apply toan annealed polymer produced in Step 7.

-   Step 7: Anneal samples of a bar or block which have been irradiated    to that dose that was identified in Step 4A as being necessary to    provide the required improvement in wear resistance, at various    time/temperature combinations, to produce a polymer with the    critical properties between those for non-remelted and remelted    materials.-   Step 8: The physical or chemical propert(ies) of interest of the    irradiated and annealed samples of the polymer are correlated with    annealing times and temperatures.-   Step 9: Using ultimate tensile strength as an example of the    physical characteristic of interest, depending on the resultant    curve for annealing time and/or temperature vs. ultimate strength,    the radiation dose required to achieve the desired wear resistance    identified in Step 4A (above) should produce a polymer with an    ultimate strength within allowable limits.

Similar consideration should be given to each of the other importantphysical and/or chemical properties by generation of individual curvesof these properties versus annealing time and/or temperature. If each ofthese properties is within allowable limits at a particular annealingtime and temperature combination, then a suitable method has beenidentified (Step 10).

If an annealing process cannot be identified that maintains theproperties within allowable limits, then the user may choose to accept alower radiation dose (Step 11), i.e., to accept less of an improvementin wear resistance. However, if a lower radiation dose (and, therefore,a greater wear rate) is acceptable, then the corresponding physical andchemical properties should again be checked for the remelted polymer(using the correlation arrived earlier in Step 4B), since these may bewithin limits at the lower radiation dose.

If the properties are within limits for the remelted polymer at thelower radiation dose, then remelting may be used instead of annealing toproduce a polymer with the desired improvement in wear resistance (Step6). If not, then the user should proceed with annealing as before (Steps7 through 10 or 11) but at this lower radiation dose.

The user may wish to progressively reduce the required amount ofradiation crosslinking (i.e., to accept still higher wear rate) until adose is identified for which all of the other properties deemedessential are within the user's required limits. The resultant doserepresents the maximum improvement in wear resistance obtainable withinthe user's criteria.

II(b) Example Applications of the Flowchart

As starting points for the flowchart, the ranges for radiation doses,remelting and annealing temperatures and times described in section “I.First Aspect of the Invention: Polymeric Compositions with IncreasedWear Resistance” and “I (A) Further Examples of the First Aspect of theInvention”, above, can be used, with regard to polymers in general, UHMWand HMW polymers in particular, and HMWPE and UHMWPE especially.

For ease of discussion, the following examples illustrate theapplication of the flowchart using UHMWPE (which also behaves similar toHMWPE) as an example of a polymer and an acetabular cup as an example ofan implant. GUR 4150 is representative of such a class of UHMWPE.Similarly, the description uses gamma radiation as an example forcrosslinking the polymer. These examples are meant to illustrate and notmeant to limit the invention.

The method described by the flowchart is applicable to other polymers,implants or other products made from such polymers, and crosslinkingmethods (examples of which are described elsewhere in this application),and methods for making an implant or product out of the preformedpolymeric composition.

From the data provided by the EXAMPLES (following sections) a number ofgeneralities were discovered that allowed simplification of the use ofthe flowchart, i.e., to minimize the amount of additional testing thatwould be required of a user wishing to apply the method to otherpolymers, or to the GUR4150 of the EXAMPLES but with variousoptimization criteria.

To establish the critical curve for the reduced in vivo wear (Step 4A),the UHMWPE bar or block is preferably irradiated in Step 2 and remeltedin Step 3, in a manner and to a dose and temperature and time asdescribed for UHMWPE in the section, “I. First Aspect of the Invention:Polymeric Compositions with Increased Wear Resistance” and “I (A)Further Examples of the First Aspect of the Invention”, above.

In step 4A, acetabular cups are machined out of the irradiated bar andwear tested under conditions suitably representative of the intended invivo application (e.g., by the method described in the EXAMPLES sectionbelow) to establish a wear vs. radiation dose response curve for thespecific polymer. EXAMPLE 5 and FIG. 22 show a wear dose-response curvefor gamma irradiated GUR 4150 UHMWPE.

Applicants discovered that it is not necessary to generate additionalwear dose-response curves for each of the many possible combinations ofannealing time and temperature. This follows from the results of EXAMPLE2. Since annealing is done at a lower temperature than remelting and,therefore, has a less marked effect on physical properties in general,it can be expected that annealing will have even less of an effect onthe wear resistance than remelting.

Another important aspect of the invention is the discovery that wearresistance of GUR 4150 was not markedly affected by remelting and,therefore, it is also not likely to be markedly affected by annealingtime and temperature. Therefore, it is expected that the radiation dosenecessary to produce the desired reduction in wear that is determinedfrom the wear dose-response curve for remelted polymer in Step 4A, willalso apply to an annealed polymer produced in Step 7. Therfore, whilethe user needs to do his own tests to establish tensile strength vs doseetc., he can rely on the wear vs dose curve developed for the remeltedmaterial, rather than running an additional set of wear curves for eachannealing condition. This represents a considerable saving inexperimental costs, since the tensile strength tests typically may becompleted in a few days (using common tensile test apparatus), but thetests of wear vs dose require months to complete (and require highlyspecialized equipment and techniques available on only a handful oflaboratories in the world).

Furthermore, if the user is working with GUR 4150, he can use the dosevs wear curve of FIG. 22 (as well as the plots of other mechanicalproperties, FIGS. 25-27) without needing to run any wear or tensiletests. Finally, if he is working with another grade of UHMWpolyethylene, he can probably use FIG. 22, since other tests have shownthat the wear resistances of these materials are very similar to GUR4150 for a given sterilization treatment. At the least, FIG. 22establishes the range on which the user may focus his wear vs. doseexperiments for other grades of UHMW polyethylene, to minimize thetesting necessary to identify the optimum dose.

For other polymers, comparable wear tests at each end of the range ofinterest for radiation dose could be applied to verify whether remeltingor annealing also does not markedly affect their wear resistance.Nevertheless, GUR 4150 is representative of UHMWPEs, especially thoseuseful for implants, in its physical and chemical properties, andapplicants have observed that other UHMWPEs, of different molecularweights and with or without calcium stearate, such as GUR 1020 (calciumstearate free, lower molecular weight grade) behaved similarly to GUR4150 in their wear resistance after irradiation sterilization in air.McKellop, H. et al., Trans. Society for Biomaterials, Vol. 20, pg. 43(1997).

Further, it has been observed that, although the starting physicalproperties of HMWPE are different from those of UHMWPE, thesedifferences will be substantially reduced after sufficient crosslinking.For example, they are almost equal after electron beam irradiationtreatment to 300 kGy (30 Mrad), for properties like gel content,swelling and strength. Streicher, R. M., Beta-Gamma 1/89: 34-43, at p.42, right col., fourth full paragraph. Even the wear properties were thesame, after the differences in the molecular arrangement between HMWPEand UHMWPE were offset by the irradiation procedure. Thus, it ispredicted that the findings based on GUR 4150 and the above discussionwould be applicable to polymers in general, and to UHMW and HMVpolymers, in particular, and especially HMWPE and UHMPE. Thus, theradiation, remelting and annealing ranges found for GUR 4150 can beapplied to polymers in general, and more preferably to HMW and UHMWpolymers, and most preferably to HMWPE and UHMWPE; and these ranges canbe used at the very least, as starting points in the flowchart fordetermining the specific ranges for other polymers, and the data in the“EXAMPLES” section below will facilitate the user in arriving at theproper conditions for GUR 4150, ASTM F648 Type 2 UHMWPE, and UHMWPE andHMWPE in general.

The following examples illustrate the use of these generalities inconjunction with the flowchart. In the first example, if the user isworking with GUR 4150, or an UHMWPE that satisfies ASTM F648 Type 2criteria in general, then, based on FIGS. 25-27, only the elongationwill fall below the ASTM limit (i.e., 300%) over the dose range ofinterest, i.e., 0 to 25 Mrad, and this occurs at about 6 Mrad. Thus, themaximum allowable dose is 6 Mrad and, from the wear vs dose plot (FIG.22), it can be seen that a 6 Mrad dose will provide a wear rate of about7 to 8 mm³ per million cycles. This is about a 78% or more reductionover the 33.1 mm³ per million cycles shown for non-remelted polyethenegamma irradiated to 3.1 Mrad in air. If this reduction in wear rate issufficient for the user's purpose, then his goal is achieved. Notehowever, that the elongation vs dose plot (FIG. 27) shows virtually thesame behavior whether the polyethylene is remelted or not, so if theabove 78% reduction is not sufficient for the user's purpose, then theuser would have no choice but to increase the radiation dose, asannealing is also not likely to affect the elongation to break, for thereasons discussed above.

In a second example, a user requires a lower limit on tensile strengthat break at 40 MPa, and wishes to produce a material with wear no morethan 1 mm³ per million cycles. The wear vs dose curve (FIG. 22) showsthat a dose of about 15 Mrad is required to produce a polyethylene withthe desired amount of wear resistance. However, the tensile strength atfracture vs dose curve shows that the tensile strength at 15 Mrad for aremelted material is about 36 Mpa. Since this is below the user'sacceptable limit of 40 Mpa, he can either use a smaller radiation doseand, therefore, accept a smaller improvement in wear rate (i.e., if hewishes to remelt his material) or he can try annealing instead ofremelting since, depending on the time/temperature combination used,annealing can be expected to produce a polymer with a value of tensilestrength between the limits indicated by the curves for non-remelted andremelted polymer (FIGS. 25 and 26). As shown on these figures, thetensile strength at 15 Mrad for a non-remelted material is about 46 Mpa,well above the user's limit of 40. So, with minimal trial and error, theuser can identify an annealing time and temperature that, when appliedto a polyethylene that has been exposed to 15 Mrad radiation, has atensile strength of the required 40 Mpa. Again, based on the wear testresults, the user knows that he does not have to re-do the wear vs dosecurve for all of the various annealing treatments he tries, in order toidentify the dose necessary to produce the desired improvement in wearresistance.

Having described the invention, the following examples are presented toillustrate and support the invention, and are not to be construed aslimiting the scope of the invention.

EXAMPLES

The nominal dose of radiation applied to implants at a commercialradiation facility typically varies within a range. Therefore, in thefollowing examples, the average gamma radiation doses are given, such asaverage gamma radiation doses of 3.3, 26.5, and 28 Mrad. The average of3.3 Mrad was arrived at by averaging the minimum and maximum doses,e.g., a minimum of 3.28 and a maximum of 3.45 Mrad. Similarly, forexample, the average of 26.5 was based on averaging a minimum of 25.14and a maximum of 27.70 Mrad; and the average of 28 was based onaveraging a minimum of 26.01 and a maximum of 30.30 Mrad.

Example 1 Effect of Radiation Atmosphere and Dose on the PhysicalProperties of UHMWPE

Experimental Details

Commercial-grade UHMWPE extruded bars (GUR 4150, Poly Hi Solidur), witha weight average molecular weight of 5-6×10 ⁶, were used as received.The 8 mm thick specimens were cut from the bars and irradiated withgamma-rays at room temperature either in ambient air or in a vacuumchamber at SteriGenics International (Tustin, Calif.) to average dosesranging from 3.3 to 250 Mrad. Radiation was delivered at a dose rate of0.2 Mrad/hr. For 250 Mrad, the dose rate was 4 Mrad/hr. Cobalt-60 wasused as a source of gamma radiation. A subset of the 8 mm thickspecimens that had been irradiated in vacuum was remelted in a vacuumoven by heating from room temperature to 145° C. slowly (at about 0.3°C./min.) and maintaining at 145° C. for one hour. After remelting, thespecimens were slowly cooled to room temperature.

The physical properties of the disk specimens before and afterirradiation and remelting were characterized by DSC, gel contentanalysis and FTIR.

Gel Content Analysis

The gel content of each material was analyzed as a function of depthfrom the surface. 100 μm thick sections (about 50 mg) were microtomedacross the specimen. Extraction of the sol-fraction was performed byboiling in p-xylene for 24 hours, with 0.5 wt % of antioxidant(2,6-di-t-butyl-4-methyl phenol) added to prevent oxidation. For highlyoxidized sections from the surface layer, which tended to break upduring boiling, the specimens were wrapped in PTFE membrane filter (0.5μm pore size) to avoid loss of gel. After extraction, the specimens werede-swollen in acetone and dried at 60° C. in a vacuum oven to constantweight. The gel fraction was determined from the ratio of the weight ofthe dried-extracted material to that of the dry non-extracted material.

Differential Scanning Calorimetry (DSC)

For DSC measurements, samples were cored and microtomed into 200 μmthick sections across the depth. Specimens (˜4 mg) were heated from 50°C. at 10° C./min in a differential scanning calorimeter (Perkin-ElmerDSC-4) to 170° C. The melting temperature was identified from the peakof the melting endotherm. Indium was used for calibration of thetemperature and heat of fusion. The heat of fusion was determined bycomparing the area under the melting endotherm to the area of fusion ofan indium sample having a known heat of fusion of 28.4 J/g, and dividedby 292 J/g, the heat of fusion of an ideal polyethylene crystal, to getthe degree of crystallinity.

Results and Discussion

As shown in FIG. 1, irradiation increased the crystallinity of the 8 mmthick specimens of UHMWPE from about 55% to 60-66%, with considerableoverlapping for the different doses. Similar changes were observed withthe samples that were irradiated in air. The gel content (i.e., theextent of crosslinking) (FIG. 2) also increased with increasingradiation dosage. Importantly, crosslinking increased markedly movingfrom the surface into the middle of each specimen, reaching about 92%for the 3.3 Mrad dose. Apparently, the oxygen present in the vacuumchamber was sufficient to cause the increased oxidation and decreasedcrosslinking of the surface layer. Thus, our method, i.e., ofirradiating a bar and machining away the surface is more effective andefficient than use of a vacuum or other low oxygen atmosphere inproducing a final product with minimal oxidation of the bearing surface.For reference (FIG. 3), chemically crosslinked polyethylene (PE) (1%peroxide, irradiated in air) (Shen, F. W. et al. J. of Poly. Sci. PartB: Poly Phys 34:1063-1077 (1996)), which exhibits very low wear, has agel content of about 90% at about 100 microns from the surface, risingto a maximum of nearly 100% in the center.

In a second phase of this example, the 8 mm thick disks that had beenirradiated in vacuum were remelted by heating to 145° C. for one hour,and slowly cooled. This reduced the peak melting temperature, the degreeof crystallinity and the crystal size. For example (FIG. 4), thecrystallinity of the 3.3 Mrad specimens was reduced from the range of60-65% to the range of 50-53% by remelting.

In addition, during remelting, residual free radicals that were formedby the irradiation apparently recombined and increased the totalcrosslinking (as evident from the increased gel content, FIG. 5).Extinguishing free radicals in this manner, in turn, further reduces theoxidation that would otherwise occur when the cups are stored on theshelf or exposed to body fluids after implantation.

The lower gel content (crosslinking) near the surface (FIG. 3) was dueto oxidation of the surface layer at the time of irradiation. Thus, itcan be expected that the polymer of the surface layer would have lesswear resistance than that in the center of the specimen. In the methodpresented in this application, this gradient would not be present, sincethe surface layer would be removed during machining of the final implantfrom the irradiated bar or block.

The crystallinity and gel content of the irradiated 8 mm thick disks,with and without remelting, are compared in FIGS. 4 and 5, respectively.

Example 2 Wear Testing of Radiation Crosslinked Cups with and withoutRemelting

Experimental Details

Six extruded bars of UHMWPE (GUR 4150), each 3 inches in diameter, wereexposed to 3.3 or 28 Mrad of gamma radiation at a dose rate of 0.2 Mradper hour in ambient air (SteriGenics, Inc., Tustin, Calif.). Two barsfor each radiation dose were then remelted by heating in an oven inambient atmosphere from room temperature to 150° C. at about 0.3° C. perminute and holding at 150° C. for five hours, and then slow-cooling toroom temperature. The crystallinity and gel content of these fourmaterials were measured across the cross section of extra samples ofeach bar using differential scanning calorimetry (DSC) and gel contentanalysis. The results are summarized in Tables 1 and 2.

Four sets of acetabular cups were machined from bars of each of the fourmaterials at a commercial machining shop (Bradford and MeneghiniManufacturing Co., Santa Fe Springs, Calif.). Each cup had a 2 inchouter diameter (O.D.) and 1.26 inch inner diameter (I.D.), and 1 inchouter radius and 0.633 inch inner radius (FIG. 6). Wear tests were runon two sets of three cups for each radiation dose that had beenremelted, and two sets of three cups for each dose that had not beenremelted. The bars were intentionally used with larger diameters thanthe final cups so that the process of machining away the outer 0.5inches of each bar removed the most oxidized, most crystalline, leastcrosslinked surface layer which is about 0.5 to 1.0 mm thick. In thismanner, the bearing surface of each cup consisted of material from nearthe center of the bar, i.e., the most crosslinked, least crystalline,least oxidized region, which is predicted to be the most wear resistant.

Since acetabular cups used in patients must first be sterilized by someacceptable means, the test cups in this study were sterilized prior towear testing using ethylene oxide at the appropriate dose for clinicalimplants. Ethylene oxide was chosen instead of additional gammairradiation (e.g., 2.5-4.0 Mrad) in order to confine the results to theeffects of the original 3.3 or 28 Mrad doses used to crosslink thematerials.

Prior to wear testing, the cups were pre-soaked in distilled water forthree weeks to minimize additional fluid absorption during the weartest, thereby making the weight loss method for wear measurement moreaccurate. For the wear test, the cups were enclosed in polyurethanemolds and pressed into stainless steel holders (FIG. 7). Each holder wasfitted with an acrylic chamber wall to contain the lubricant. Thechambers were mounted on the hip simulator wear machine, with each cupbearing against a ball of cobalt-chromium alloy (conventional hipreplacement femoral balls were used, with implant-quality surfacefinish). The ball-cup pairs were subjected to a physiological cyclicload with a peak load of about 2000 Newtons (Paul, J P., “Forcestransmitted by joints in the human body”. In Lubrication and Wear inLiving and Artificial Human Joints. Proc Instn Mech Engrs 1967;181 Part3J:8-15) and the cups were oscillated against the balls through abi-axial 46° arc at 68 cycles per minute. Each test station on thesimulator (FIG. 7) contains a self-centering unit 5, the acetabular cup6, a dual axis offset drive block 7, a test chamber 8, serum lubricant 9and a femoral ball 10. The arrow indicates the direction of the computercontrolled simulated physiological load applied to the simulated hipjoint.

During the test, the bearing surfaces were kept immersed in bovine bloodserum to simulate lubrication in the human body. Sodium azide at 0.2%was added to the serum to retard bacterial degradation, and 20 mMethylenediaminetetraacetic acid (EDTA) was added to preventprecipitation of calcium phosphate onto the surface of the balls(McKellop, H. and Lu, B., “Friction and wear of Polyethylene-metal andPolyethylene-ceramic Hip Prostheses on a Joint Simulator, Transactionsof the Fourth World Biomaterials Congress, Berlin, April 1992, p. 118).A polyethylene skirt covered each test chamber to minimize airbornecontaminants.

At intervals of 250,000 cycles, the cups were removed from the machine,rinsed, inspected under light microscopy and replaced in freshlubricant. At intervals of 500,000 cycles, the cups were removed,cleaned, dried and weighed to indicate the amount of wear. Afterinspection under light microscopy, the cups were replaced on the wearmachine with fresh lubricant and testing was continued to a total ofthree million cycles. One million cycles is approximately the equivalentof one year's walking activity of a typical patient.

The weight loss was corrected for the effects of fluid absorption (whichmasks wear) by increasing the apparent weight loss of the wear test cupsby the mean weight gain of three control cups of each material that werealso immersed in serum and cyclically loaded on a separate frame, butwithout oscillation. The corrected rate of weight loss was converted tovolume loss by dividing by the approximate density of UHMWPE (0.94gm/cc). The mean weight loss (after soak correction) and the standarddeviation was calculated for each of the four types of materials at eachweighing interval. The wear rate of each cup was calculated by applyinglinear regression to the wear data for the entire three million cycles.The mean wear rates and standard deviations also were calculated foreach type of material.

Results

FIG. 8 shows the soak-corrected wear (volume loss) of three cups of eachmaterial as a function of wear cycles. FIG. 9 shows the average wear(volume loss) of three cups of each material as a function of wearcycles. The individual wear races and the mean values for each type ofmaterial are listed in Table 3. The most wear occurred with the cupssubjected to 3.3 Mrad without remelting. These averaged 21.1 mm³ permillion cycles.

The wear of the cups subjected to 3.3 Mrad with remelting averaged 18.6mm³ per million cycles, or 12% lower wear than for the non-remelted 3.3Mrad cups. The cups subjected to 28 Mrad had much lower wear rates thanthe 3.3 Mrad cups, and the rates were similar, whether or not thematerial had been remelted. That is, the average wear rate of thenon-remelted 28 Mrad cups was about 1.2% that of the non-remelted 3.3Mrad controls, and the average wear rate of the remelted 28 Mrad cupswas about 1.7% of the same controls.

Discussion

The results of the wear test clearly demonstrated the improved wearresistance of the UHMWPE acetabular cups that resulted from exposure to28 Mrad gamma radiation. Apparently, the crosslinking generated by thehigher radiation dose reduced the wear rates to less than a few percentof the control value (3.3 Mrad). The minimum amount of wear debrisnecessary to induce clinically significant osteolysis and other problemsin a specific patient has not been established, and it may vary amongpatients. Nevertheless, a material which reduces the wear rate to thevery low levels exhibited by the 28 Mrad cups in this study would bevery likely to provide a large margin of safety over currently usedmaterials.

The wear curves for both of the 28 Mrad specimens (FIGS. 8 & 9) wereslightly negative on the first weighing at 0.5 million cycles. This wasmost likely due to a slight under-correction for fluid absorption (thatis, the wear test cups absorbed slightly more water than the soakcontrols, and the error between the two was greater than the weight lossdue to wear, producing a negative wear value). If this assumption iscorrect, then the overall wear rates for the two 28 Mrad sets weresomewhat smaller, and possibly closer together, than the valuesindicated in Table 3.

Example 3 Artificial Aging of Radiation-Crosslinked UHMWPE Materials

Six UHMWPE (GUR 4150) extruded bars (3″ diameter) were gamma irradiatedin air, three bars each at 3.3 or 28 Mrad, at a dose rate of 0.2Mrad/hour. For each radiation dose, two bars were then remelted byheating in an oven at ambient atmosphere from room temperature to 150°C. at about 0.3° C./min, holding at 150° C. for 5 hours and slowlycooling to room temperature, and the third bar was not remelted. A 13 mm(0.5 inch) layer of the outer diameter of the treated (remelted) anduntreated (non-remelted) bars was machined away to remove the mostoxidized, least crosslinked surface layer. The bars were used to producespecimens for the artificial aging tests described here and for the weartests described in EXAMPLE 2.

To examine the effect of artificial aging on these four materials (3.3and 28 Mrad, remelted and not remelted), 8 mm thick disks were cut fromthese 2 inch diameter cores and were heated in an oven slowly (˜0.2°C./min) to 80° C. at ambient atmosphere and held at 80° C. for 10, 20 or30 days. In addition, one acetabular cup for each of the four conditions(3.3 and 28 Mrad, remelted and not remelted) that had been fabricated atthe same time as the wear test cups of EXAMPLE 2 and stored in air forabout 5 months was cut into four pieces and aged at 80° C. for the sameperiods.

The gel content analysis and DSC method are as described in EXAMPLE 1,above.

Fourier Transform Infrared Spectroscopy (FTIR)

FTIR measurements were performed on the above specimens. Segments about5 mm wide were cut from each polyethylene specimen and the segments weremicrotomed into 200 μm thick slices. The oxidation profiles, asindicated by the carbonyl concentration, were measured using a MattsonPolaris FTIR (model IR 10410) with a Spectra-Tech IR plan microscope.Spectra were collected in 100 μm steps from the surface to the middle ofthe specimen, using 64 scans summation at a resolution 16 cm⁻¹ with aMCT (Mercury Cadmium Telluride) detector. The carbonyl groupconcentration was indicated by the ratio of the peak height of theketone absorption band at 1717 cm⁻¹ to the height of the reference bandat 2022 cm⁻¹ (—CH₂— vibration).

Results

The oxidation profiles as a function of depth are shown in FIGS. 10-13.As shown in FIG. 10 for the 3.3 Mrad, non-remelted material, oxidationincreased with increasing aging time. In contrast, the 3.3 Mrad,remelted material (FIG. 11) showed almost no oxidation for 10 and 20days aging, but some oxidation for 30 days aging. However, the oxidationpeak at the surface with remelting was about 50% of that at the surfacewithout remelting (FIG. 10). For the 28 Mrad, non-remelted UHMWPE (FIG.12), the oxidation showed a greater increase with increasing aging timethan the 3.3 so Mrad, un-remelted material. Again, oxidation was muchlower with remelting, i.e., the 28 Mrad, remelted UHMWPE (FIG. 13)essentially exhibited no oxidation after 20 days aging (FIG. 13), andthe oxidation peak at the surface after 30 days was only about ⅓ thatwithout remelting (FIG. 12).

Similarly, with the acetabular cups stored in air for 5 months and thenaged for 20 days at 80° C., the remelted materials (3.3 or 28 Mrad)showed no oxidation (FIG. 14), while the non-remelted cups (3.3 or 28Mrad) showed substiantial oxidation (FIG. 14), especially for 28 MradUHMWPE, and with a subsurface oxidation peak in both non-remeltedmaterials.

Since crosslinking of UHMWPE reduces its solubility, the percent ofundissolved material (gel content) is an indirect indication of theamount of crosslinking. The gel content as a function of depth forvarious conditions are shown in FIGS. 15 to 18. As shown in FIG. 15 for3.3 Mrad, non-remelted material, the gel content (i.e., crosslinking)decreased with increasing aging time. There was a strong gradient of gelcontent in the highly oxidized surface regions after 30 days aging,i.e., increasing from a minimum on the surface to a maximum about 2 mmbelow the surface. Near the surface, the gel content was highest (91%)in the un-aged specimen, and decreased with increasing aging time toless than about 5% in the same region for the 30 day aged specimen. Incontrast, the remelted materials (FIG. 16) showed much less reduction ingel content in the surface regions than the non-remelted materials. Thatis, comparison of FIG. 17 (28 Mrad, non-remelted) and FIG. 18 (28 Mrad,remelted) showed that the remelted UHMWPE had much higher retention ofgel content (i.e., crosslinking).

The results of the DSC measurements indicated the degree ofcrystallinity as a function of depth for various materials aged for 30days at 80° C., as shown in FIG. 19. Near the surface, the degree ofcrystallinity was 83% for the 28 Mrad, non-remelted material afteraging, compared to 65% before aging. The high level of crystallinity andincreased brittleness of the surface zone of the aged material oftenresulted in fragmentation of a layer about 1 mm thick duringmicrotoming. In contrast, the 28 Mrad remelted material showed lessincrease in crystallinity in the surface regions due to aging, and nobrittle zone was observed. Similarly, due to aging, the 3.3 Mradnon-remelted material exhibited an increase in crystallinity from 60% toabout 78%, and the surface layer was again brittle, although not asbrittle as with the 28 Mrad, non-remelted material.

Discussion

Irradiation of UHMWPE produces crosslinking, chain scission and theformation of free radicals. If oxygen is present, it may react with thefree radicals to form oxidized species, leading to additional chainscission (reduction in molecular weight) and an increase incrystallinity. Since polymer crystallites melt and become amorphousabove the melting temperature, molecular chain movements and rotationsare increased, favoring the recombination of free radicals. The resultsof the present experiments showed that remelting at 150° C. apparentlycaused the residual free radicals to decay and/or to recombine to formcrosslinks, leading to an increased gel content. Therefore, remelting isan effective way to extinguish free radicals, making the material lesssusceptible to long-term oxidation and potentially improving thelong-term wear resistance, as evident from the results of the artificialaging experiments, where there was much less oxidation of the remeltedmaterials.

For a crosslinked polymer, oxidative degradation cleaves the moleculesand leads to a reduction in gel content. This was evident in the presentexperiments from the reduced gel content after aging, particularly withthe non-remelted materials (FIGS. 15 to 18). That is, the distributionof oxidation, as indicated by the profiles measured by FTIR, was inverseto the gel content within the material; the higher the oxidation, thelower the gel content (crosslinking). Since remelting extinguishes freeradicals and increases gel content, thereby reducing the susceptibilityto oxidation, the remelted materials (3.3 and 28 Mrad) had a muchgreater gel content after artificial aging than the non-remeltedmaterials.

An appropriate amount of crosslinking of UHMWPE can improve its wearresistance. The high level of crosslinking in the UHMWPE caused by the28 Mrad gamma irradiation, as evident from the high gel content (EXAMPLE2), apparently contributed to the much greater wear resistance exhibitedby the acetabular cups tested in EXAMPLE 2. In addition, as shown inEXAMPLE 3, remelting of the irradiated UHMWPE markedly reduced theresidual free radicals, rendering the material much more resistant tosubsequent oxidation and, therefore, resistant to a reduction incrosslinking, which can be of substantial benefit for implants inlong-term clinical use.

Example 4 Wear Testing of Irradiated Cups with and without ArtificialAging

Materials and Methods

The wear testing of irradiated cups with and without remelting wasdescribed in EXAMPLE 2. Effects of artificial aging on the physicalproperties of irradiated UHMWPE, with and without remelting, weredescribed in EXAMPLE 3. To examine the resistance of crosslinked cups tothermal-induced oxidation, and the effect of such oxidation on the wearof irradiated cups with and without remelting, two acetabular cups foreach of the four conditions (3.3 and 28 Mrad, remelted and not remelted)that had been wear tested for 3 million cycles as described in EXAMPLE2, were heated in an oven slowly (−0.2° C./min) to 80° C. at ambientatmosphere and held at 80° C. for 20 days, with one acetabular cup foreach of the four conditions being stored in ambient air. The oxidationprofile after 20-day aging for each condition was shown in FIG. 14,EXAMPLE 3.

Prior to wear testing, the cups were pre-soaked in distilled water forfour weeks to minimize additional fluid absorption during the wear test,thereby making the weight loss method for wear measurement moreaccurate. The details for the wear test were described in EXAMPLE 2.

Results

FIG. 20 shows the combined soak-corrected wear (volume loss) for thecups before aging (3.3 and 28 Mrad, remelted and not remelted) duringthe first 3 million cycles (same data as EXAMPLE 2) and for the samecups, after two cups of each material had been artificially aged, from 3to 7 million cycles. The individual wear rates and the mean values foreach type of material, calculated by linear regression, are listed inTable 4.

All cups subjected to 3.3 Mrad with remelting showed comparable wearrates, whether or not the material had been remelted or remelted andaged. Wear was negligible for all of the cups subjected to 28 Mrad,whether or not these were remelted, and whether or not they were aged.

Discussion

The results of the wear test clearly demonstrated the improved wearresistance of the UHMWPE acetabular cups that resulted from exposure to28 Mrad gamma radiation. Apparently, the minor oxidation at the surface(FIG. 14) of the highly crosslinked acetabular cups (28 Mrad, withoutremelting) induced by the artificial aging, had very limited effect onthe wear resistance. Although a substantial oxidation peak occurredabout 0.4 mm below the surface, because of the very high wear resistanceof the 28 Mrad cups, the total penetration due to wear was too shallowto reach this sub-surface oxidized zone, even after 4 million cycles.

For the non-remelted 3.3 Mrad cups, subsurface oxidation, peaking atabout 1 mm below the surface (FIG. 14), occurred after aging in air at80° C. for 20 days. Since the total depth of penetration of these cupswas about 300 microns (at 7 million cycles), the full effect of thissubsurface oxidation would not become apparent until a much largernumber of wear cycles.

Nevertheless, the sub-surface oxidation in the non-remelted cups(EXAMPLE 3, particularly for the 28 Mrad specimen) leads to reducedmolecular weight, a reduction in crosslinking (as indicated by gelcontent) and an increased crystallinity and brittleness, all of whichcan contribute to reductions in mechanical properties such as fatiguestrength and, eventually, a reduction in wear resistance. Althoughremelting had no apparent effect on the wear resistance of the aged cupsin the present example, the elimination of free radicals by remeltingimproves the long-term resistance to oxidation, thereby improving thelong-term wear resistance in vivo.

Example 5 Wear Testing of Gamma-Irradiated UHMWPE with Multiple Doses

Materials and Methods

In EXAMPLE 2, we demonstrated the improved wear resistance of UHMWPEacetabular cups that resulted from exposure to 28 Mrad gamma radiation,as compared to cups irradiated to 3.3 Mrad. The average wear rate of the28 Mrad cups was less than 2% of that of the 3.3 Mrad cups (i.e., a dosewithin the normal 2.5 to 4.0 Mrad range used to sterilize implants). Toexamine the wear as a function of radiation dose and, thereby, determinean optimum dose for reducing wear, extruded bars of GUR 4150 UHMWPE, 3″diameter×15″ long, were gamma irradiated in air, three bars at each doseof 4.5, 9.5, 14.5, 20.2 or 24 Mrad (SteriGenics, Inc., Corona, Calif.),at a dose rate of 0.45 Mrad/hour. Additional bars were irradiated in airto 50 or 100 Mrad (SteriGenics Inc., Tustin, Calif.), at a dose rate of0.67 Mrad/hour. For each radiation dose, two bars were then remelted byheating in an oven in ambient atmosphere from room temperature to 150°C. at about 0.3° C./min, holding at 150° C. for 5 hours and thenslowly-cooled to room temperature, with the third bar not beingremelted. The irradiated-remelted bars were used to produce acetabularcups for the wear tests.

Seven sets of acetabular cups were machined from the irradiated-remeltedbars for each of the seven doses at a commercial machining shop(Bradford and Meneghini Manufacturing Co., Santa Fe Springs, Calif.).Each cup had a 2″ O.D. and 1.26″ I.D., with 1″ outer radius and 0.63″inner radius (FIG. 6). Wear tests were run on the remelted specimens,using two cups for each radiation dose from 4.5 to 24 Mrad, and one cupeach for 50 and 100 Mrad. The bars were intentionally used with largerdiameters than the final cups so that the process of machining away theouter layer of each bar, about 0.5 inch thick, effectively removed themost oxidized, most crystalline, least crosslinked surface layer (about0.5 to 1.0 mm). In this manner the bearing surface of each cup consistedof material from near the center of the bar, i.e., the most crosslinked,least crystalline, least oxidized region, which was expected to be themost wear resistant.

Because acetabular cups used in patients must first be sterilized bysome acceptable means, the test cups in this study were sterilized priorto wear testing using ethylene oxide at the appropriate dose forclinical implants. Ethylene oxide was chosen instead of additional gammairradiation (e.g., 2.5-4.0 Mrad) in order to focus the results on theeffects of the radiation doses used to crosslink the materials. Prior towear testing, the cups were pre-soaked in distilled water for four weeksto minimize additional fluid absorption during the wear test, therebymaking the weight loss method for wear measurement more accurate. Thedetails for the wear test method were described in EXAMPLE 2.

Results

FIG. 21 shows the soak-corrected wear (volume loss) of each material(three cups for 3.3 Mrad from EXAMPLE 2, two cups each for radiationdose from 4.5 to 24.5 Mrad, and one cup each for 50 and 100 Mrad). Theindividual wear rates, determined by linear regression, and the meanvalues for each type of material are listed in Table 5. At about 2.1million cycles, there was a temporary overloading of the test cups, dueto a malfunction of the computer controller. Although this overload hadonly a minor effect on the wear rates of the cups, the cup irradiated to100 Mrad cracked and was, therefore, removed from the test.

FIG. 22 shows the average wear rate (volume loss from 1 to 5 million) ofeach type of material, that had been remelted (denoted in the figure bydarkened circles) and that had not been re-melted (denoted in the figureby an open circle), as a function of dose.

The wear of the cups subjected to 3.3 or 4.5 Mrad with remeltingaveraged 17.5 or 9.3 mm³ per million cycles, respectively, showing about13% or 54% lower wear than for the 3.3 Mrad non-remelted cups (20.1 mm³per million cycles). In contrast, the wear rate of the 9.5 Mrad remeltedcups averaged 2.2 mm³ per million cycles, i.e., about 89% lower than forthe 3.3 Mrad non-remelted cups. For radiation doses greater than 9.5Mrad, minimal systematic wear occurred, such that, compared to that with3.3 Mrad non-remelted cups, the wear rates were about 94% lower for the14.5 Mrad remelted cups, and minimal wear (>99% reduction) for the 20.2Mrad remelted cups.

“Negative” wear rates were calculated for the cups given 24 Mrad orgreater doses. Apparently, these cups absorbed more water than the soakcontrol cups, and the error between the two was greater than the weightloss due to wear, giving a net gain in weight.

Discussion

The results clearly demonstrated that the wear resistance of UHMWPEacetabular cups were improved substantially with increasing radiationdose over the range of 4.5 to 9.5 Mrad (i.e., with increasingcrosslinking), such that wear was too small to accurately quantify fordoses exceeding about 20 Mrad. Since, in addition to improving wearresistance, radiation induced crosslinking may degrade other physicalproperties, such as elongation to failure and fatigue strength, thedose-response curve developed in the present example provides theopportunity to select an optimum dose, i.e., one that provides thedesired amount of improvement in wear resistance with a minimumreduction in other physical properties. The procedure for arriving atthe choice of dose for a particular in vivo application is described inthis application.

UHMWPE acetabular cups that had been compression molded and then exposedto 3.1 Mrad gamma radiation in air but were not thermally treated (i.e.,typical of commercially used implants over the past two decades), showedan approximate wear rate of 33.1 mm³/million cycle using the procedureof the wear test described in EXAMPLE 2, above. When compared to theseconventional UHMWPE acetabular cups, the acetabular cups of the presentinvention (i.e., irradiated bar stock, remelted and machined into cups)show the following percentage reduction in wear rate: for the 3.3 Mradremelted acetabular cup from EXAMPLE 2, above (about 47% reduction inwear rate); 4.5 Mrad remelted acetabular cup from EXAMPLE 5, above(about 72% reduction in wear rate); 9.5 Mrad remelted acetabular cupfrom EXAMPLE 5, above (about 93% reduction in wear rate).

Example 6 Physical Characterization of Gamma-Irradiated UHMWPE with orwithout Remelting

Materials and Methods

The materials for physical characterization were the same as the weartested materials described in EXAMPLE 5. The materials included UHMWPEextruded bars (3″ in diameter) gamma irradiated to 3.3, 4.5, 9.5, 14.5,20.2, 24, 50 and 100 Mrad, with or without remelting, and thenon-irradiated bars. 8 mm thick disks were cut out of irradiated barswith or without remelting, and sterilized with ethylene oxide. Thespecimens for DSC and swelling measurements were cut out of the centerof the 8 mm thick disks. The DSC measurement for crystallinity andmelting temperature with sample weighing about 4 mg was described inEXAMPLE 1. For swelling measurements, 1 mm thick sheet weighing about0.5 gram was cut out of the center of the 8 mm thick disk, andextraction of the sol-fraction was performed in boiling p-xylene for 72hours, with 0.5 wt % antioxidant (2,6-di-t-butyl-4-methyl phenol) beingadded to prevent oxidation. After extraction, the gel was transferred tofresh p-xylene and allowed to equilibrate at 120° C. for 2 hours. Theswollen gel was then quickly transferred to a weighing bottle, coveredand weighed. The data was obtained as the average of five measurements.After measurements, samples were deswollen in acetone and then dried at60° C. in a vacuum oven to a constant weight. The gel fraction wasdetermined as the ratio of the weight of the dried extracted to theinitial dry non-extracted network. The degree of swelling was calculatedas the ratio of the weight of the swollen gel to the dried extractedgel. The degree of swelling was used to calculate the network chaindensity, number-average molecular weight between crosslinks andcrosslink density, according to the theory of Flory and Rehner (Shen etal., J. Polym. Sci., Polym. Phys., 34:1063-1077 (1996)). For examiningthe oxidation profiles of the extruded bars irradiated and remelted inair, a two hundred micron thick section was microtomed perpendicular tothe bar surface and examined by FTIR as a function of depth from the barsurface.

Results and Discussion

The melting temperature and crystallinity for non-irradiated, andirradiated (with and without remelting) materials are shown in Table 6.The degree of swelling, average molecular weight between crosslinks,crosslink density and gel content are shown in Table 7. Afterirradiation, the melting temperature and crystallinity increased,ranging from 135.3 to 140.2° C., and about 60 to 71%, respectively, overthe dose range studied. Remelting of the irradiated bars resulted inreductions in the melting temperature and crystallinity, ranging fromabout 131 to 135° C., and about 51 to 53%, respectively.

As shown in Table 7, with increasing radiation dose, the degree ofswelling and average molecular weight between crosslinks decreased,while the crosslink density increased. The gel content, in general,increased with radiation dose, but reached a plateau region at about 9.5Mrad. With remelting, the degree of swelling and average molecularweight between crosslinks for bars irradiated up to 9.5 Mrad weresignificantly reduced, but remained almost unchanged after 9.5 Mrad. Thecrosslink density increased, after remelting, with dose up to 9.5 Mradand then remained almost unchanged. The gel content, generally,increased after remelting.

The oxidation profiles for the 9.5 and 24 Mrad materials, afterremelting at 150° C. in air for 5 hours, as a function of depth from thebar surface are shown in FIG. 24. The results clearly showed that theoxidation drops tremendously within 1 mm, and the most oxidized layer isabout 1 mm deep below the surface, after irradiation and remelting inair.

Example 7 Tensile Properties of Gamma-Irradiated UHMWPE at VariousDoses, with or without Remelting

Materials and Methods

The materials for tensile test are the same as the wear tested materialsdescribed in EXAMPLE 5, above. The materials included UHMWPE extrudedbars (3″ in diameter) gamma irradiated to 4.5, 9.5, 14.5, 20.2, and 24Mrad, with or without remelting, and non-irradiated bars. Five tensilespecimens each was machined out of the center of the 3″ diameter barsaccording to ASTM F648-96 and D-638 (type IV). Tensile tests wereperformed using an servo-hydraulic tensile test machine at speed of 2inches/min.

Results and Discussion

The tensile strength at yield, elongation, and tensile strength(ultimate) at breaks are shown in Table 8. The average tensileproperties as a function of radiation dose are shown in FIGS. 25-27. Thetensile strength at yield after irradiation was higher than that ofnon-irradiated material, and slightly increased with radiation dose.Remelting of the irradiated bars resulted in a reduction in tensilestrength at yield, and the strength remained almost constant over thedose range studied (FIG. 25). The tensile strength (ultimate) andelongation at break decreased with increasing doses (FIGS. 26-27).Remelting resulted in further reduction in ultimate tensile strengthover the dose range. However, remelting had almost no effect on theelongation at break over the same dose range.

All publications and patent applications mentioned in this Specificationare herein incorporated by reference to the same extent as if each ofthem had been individually indicated to be incorporated by reference.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity andunderstanding, it will be obvious that various modifications and changeswhich are within the skill of those skilled in the art are considered tofall within the scope of the appended claims. Future technologicaladvancements which allows for obvious changes in the basic inventionherein are also within the claims. TABLE 1 3.3 Mrad Before remeltingAfter remelting Distance peak melting degree of peak melting degree offrom surface temperature crystallinity gel content temperaturecrystallinity gel content (mm) (° C.) (%) (%) (° C.) (%) (%) 34.8-35135.3 59.6 91 131.4 52.5 94.7 35.8-36 135.4 60.2 91 131.5 51.2 94.736.8-37 135.3 60.5 91 131.4 51.9 94.7 37.8-38 135.3 60 91.1 131.3 52 95(center)

TABLE 2 28 Mrad Before remelting After remelting Distance peak meltingdegree of peak melting degree of from surface temperature crystallinitygel content temperature crystallinity gel content (mm) (° C.) (%) (%) (°C.) (%) (%) 34.8-35 139.8 65.1 95.8 135 52 97.7 35.8-36 139.8 64.2 95.8134.8 52.1 97.7 36.8-37 139.7 64.5 95.8 134.9 52.5 97.7 37.8-38 139.765.3 95.8 134.9 52.7 97.7 (center)

TABLE 3 Wear Rate Mean Wear (mm³/million Rate ± Std Cup # Materialcycles) Deviation N11 3.3 Mrad 20.8 21.1 ± 0.3  N16 Not 21.2 N17remelted 21.4 R21 3.3 Mrad 17.7 18.6 ± 1.3  R26 Remelted 20.1 R27 18.0N35  28 Mrad 0.29 0.25 ± 0.03 N31 Not 0.24 N32 remelted 0.24 R48  28Mrad 0.36  0.36 ± 0.001 R45 Remelted 0.35 R49 0.36

TABLE 4 0-3 Million Cycles (non-aged) 3-7 Million Cycles Wear Rate MeanWear Wear Rate Mean Wear (mm³/million Rate ± Std (mm³/million Rate ± StdCup # Material cycles) Deviation Conditions cycles) Deviation N11 3.3Mrad 20.8 21.1 ± 0.3  non-aged 21.2 — N16 Not 21.2 aged 21.5  21.8 ± 0.5N17 remelted 21.4 aged 22.2 R21 3.3 Mrad 17.7 18.6 ± 1.3  non-aged 17.5— R26 Remelted 20.1 aged 19.2  19.8 ± 1.0 R27 18.0 aged 20.5 N35  28Mrad 0.29 0.25 ± 0.03 non-aged 0.03 — N31 Not 0.24 aged −0.47 −0.71 ±0.3 N32 remelted 0.24 aged −0.93 R48  28 Mrad 0.36  0.36 ± 0.001non-aged 0.47 — R45 Remelted 0.35 aged 0.08 −0.06 ± 0.2 R49 0.36 aged−0.20

TABLE 5 (1-5 million cycles) Mean Wear Wear Rate Rate ± SD (mm³/ (mm³/Cup # Material million cycles) million cycles)  N11  3.3 Mrad Notremelted 20.46 20.12 ± 0.7*  N16 19.32 N17 20.59 R21  3.3 Mrad Remelted17.04 17.51 ± 0.48* R26 18.0 R27 17.49 RA2  4.5 Mrad Remelted 9.93 9.28± 0.92 RA3 8.63 RB3  9.5 Mrad Remelted 2.39 2.22 ± 0.24 RB6 2.05 RC514.5 Mrad Remelted 1.26 1.17 ± 0.13 RC6 1.08 RD1 20.2 Mrad Remelted 0.260.12 ± 0.2  RD6 −0.02 RE3   24 Mrad Remelted −0.49 −0.59 ± 0.13  RE4−0.68 RF2   50 Mrad Remelted −0.8 — RG1  100 Mrad Remelted −6.88** —*The wear data of the 3.3 Mrad materials in Example 2.**The wear rate in the period of 1-2 million cycles.

TABLE 6 Non-remelted Remelted Melting point Crystallinity Melting pointCrystallinity Samples (° C.) (%) (° C.) (%) Non-irrad. 133.8 55 — —  3.3Mrad 135.3 ± 0.1 60.1 ± 0.4 131.4 ± 0.1 51.8 ± 0.6  4.5 Mrad 136.2 ± 0.265.8 ± 1.6 131.6 ± 0.2 52.0 ± 1.3  9.5 Mrad 137.1 ± 0   67.1 ± 2.2 134.8± 0.2 53.3 ± 2.1 14.5 Mrad 137.5 ± 0.2 69.6 ± 1.6 135.0 ± 0.1 53.0 ± 1.520.2 Mrad 137.4 ± 0.1 70.8 ± 2.8 135.3 ± 0.1 52.1 ± 1.8   24 Mrad 137.9± 0.3 68.0 ± 1.3 135.2 ± 0.1 51.7 ± 1.2   50 Mrad 138.9 ± 0.2 67.0 ± 1.3135.2 ± 0   52.8 ± 0.2  100 Mrad 140.2 ± 0.3 66.3 ± 2.7 130.8 ± 0.2 52.3± 1.7

TABLE 7 Non-remelted Remelted M.W. M.W. between Crosslink Gel betweenCrosslink Gel Degree of crosslinks density content Degree of crosslinksdensity content Samples swelling (g/mol) (mol %) (%) swelling (g/mol)(mol %) (%)  3.3 Mrad 5.29 8400 0.17 94.7 3.21 2500 0.56 98.1  4.5 Mrad3.57 3500 0.40 97.8 3.15 2400 0.58 98.4  9.5 Mrad 2.82 1900 0.74 98.62.54 1400 1.0 98.9 14.5 Mrad 2.35 1100 1.27 98.7 2.36 1100 1.27 99.220.2 Mrad 2.27 1000 1.40 98.8 2.25 1000 1.40 99.2   24 Mrad 2.17 9001.56 98.7 2.24 1000 1.40 99.2   50 Mrad 1.92 600 2.33 98.7 2.17 900 1.5699.1  100 Mrad 1.71 400 3.50 98.6 1.71 400 3.50 98.5

TABLE 8 Tensile Strength Tensile Strength Elongation Materials at Yield(MPa) at Break (MPa) at Break (%) Non-irradiated 23.3 ± 0.11 52.1 ± 4.78356 ± 23 Without remelting  4.5 Mrad 24.9 ± 0.33 46.9 ± 2.91 314 ± 12 9.5 Mrad 25.3 ± 0.12 47.6 ± 2.76 251 ± 8  14.5 Mrad 25.7 ± 0.25 46.4 ±1.20 213 ± 5  20.2 Mrad 26.2 ± 0.27 40.2 ± 2.72 175 ± 7    24 Mrad 26.4± 0.23 40.0 ± 5.42 164 ± 17 After remelting  4.5 Mrad 21.5 ± 0.33 45.6 ±8.89 309 ± 20  9.5 Mrad 21.3 ± 0.60 43.2 ± 2.80 252 ± 8  14.5 Mrad 21.8± 0.29 36.8 ± 1.72 206 ± 9  20.2 Mrad 21.9 ± 0.18 34.3 ± 3.61 185 ± 8   24 Mrad 21.7 ± 0.25 32.3 ± 2.81 160 ± 19

1. A preformed polymeric composition comprising a crosslinked thermallytreated polymer.
 2. The composition of claim 1, wherein the compositionpossesses one or more of the following characteristics: degree ofswelling of between about 1.7 to about 5.3; molecular weight betweencrosslinks of between about 400 to about 8400 g/mol; and a gel contentof between about 95 to about 99%.
 3. The composition of claim 1, whereinthe preformed polymeric composition is crosslinked by gamma radiation ata dose from about 1 to about 100 Mrad.
 4. The composition of claim 3,wherein the dose is from about 5 to about 25 Mrad.
 5. An in vivo implantcomprising a crosslinked and remelted polymer. 6 to
 30. (canceled).